Increasing evidence indicates that antigen-antibody complexes are involved in maintaining the chronic inflammation of joints in rheumatoid arthritis. Self-associating IgG-rheumatoid factors, first described on the molecular level in this laboratory, may be the major antigen-antibody system in rheumatoid arthritis. During the proposed work the antigenic determinants for self-association of IgG-rheumatoid factors will be defined on the Fc region of IgG molecules by protein fragmentation and immunochemical techniques. Idiotypic antigenic determinants will be sought and characterized on these unique antibody molecules by immunochemical methods. Immune complexes from synovial fluids of patients with rheumatoid arthritis will be examined qualitatively and quantitatively for several antigen-antibody systems, including the presence of IgG-rehumatoid factors. Radioimmunoassays and other immunochemical methods will be used in these studies. The potential role of self-associating IgG-rheumatoid factors in fluid phase or bound to articular cartilage, in generation of inflammation via activation of complement or activation of monocytes will be determined. Antigens cross-reacting with IgG-rheumatoid factor and animal models for self-association of IgG-rheumatoid factors will be sought.